Progression of type 2 diabetes: The role of pharmacogenetic interactions

Abstract

The overall aim of this PhD project is to contribute to the knowledge on how pharmacogenetic interactions can affect the progression of type 2 diabetes. In particular, we wish to investigate the progression of type 2 diabetes based on initiation, type and intensification of anti-diabetic treatment.

We wish to use genome-wide association analyses to identify genetic variants related to progression of type 2 diabetes measured as time from diagnosis to start of insulin treatment as well as time to first cardiovascular event. We will use genotyping data from 4 phenotypical well-described cohorts and biobanks of Danish individuals. The cohorts included are The Diet, Cancer and Health cohort (DCH), The Danish Centre for Strategic research in type 2 Diabetes (DD2) study, The Danish Addition cohort (Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-detected Diabetes in Primary Care) and The Copenhagen Insulin and Metformin Trial (CIMT).Furthermore, we will participate in an international collaboration performing genome-wide association analyses in a large cohort of T2D patients in cooperation with The Medical Research Institute, University of Dundee, Scotland. We will use data from the DD2 cohort for replication analyses. We expect that by identifying novel genetic variants associated with disease progression in T2D and development of cardiovascular complications, the proposed project will contribute to the understanding of pharmacogenetic interactions and their role in disease progression, which might lead to improved treatment effectiveness, and better patient compliance and quality of life.

Formål

1. To determine genetic variants associated with disease progression of type 2 diabetes through genome-wide association studies.

• To determine specific genetic variants associated with development of atherosclerosis in the carotid arteries

2. To determine genetic variants associated with progression in vascular complications in patients with type 2 diabetes.

Studiepopulation

Inclusion criteria: Type 2 diabetics with prescription data from diagnose to start of insulin treatment.

Exclusion criteria: Patients with prescription of antidiabetic medicine but no diabetes diagnose. Patients with start of insulin within one year of diabetes diagnose. Patients with no baseline values.  

Artikler

• Niazi (2019) Increased frequency of rare missense PPP1R3B variants among Danish patients with type 2 diabetes. PloS one.
• Sun (2019) Sequencing reveals protective and pathogenic effects on development of diabetes of rare GLIS3 variants. PloS one.

Finansiering

Danish Diabetes Academy
Novo Nordisk Fundation Center for Basic Metabolic Research